Antibody-mediated Rejection - an Ounce of Prevention is Worth a Pound of Cure

07:25: Detection and Identification of Alloantibodies circa 2010: Myths and Realities

Howard M. Gebel, Emory University Hospital, Atlanta, USA

Testing for HLA antigens and antibodies has evolved to the point where typing, screening and crossmatching assays are exquisitely sensitive and specific. The development of tests using solid-phase matrices coated exclusively with HLA class I or class II antigens permits the identification of HLA antibodies with a specificity and sensitivity not previously possible. Similarly, implementation of molecular typing methods has led to the fine resolution of HLA antigens and characterization of allelic variants. The current question is how this wealth of information is best utilized. Advances in HLA technology have resulted in two recent changes within the transplant community, namely 1) the mandated reporting of calculated PRA (cPRA) values (an objective result based on HLA antigen frequencies) and 2) implementation of the virtual crossmatch (vXM) to categorize potential donor:recipient combinations as compatible or incompatible.The vXM predicts the crossmatch to be positive or negative based on the presence of HLA class I and/or class II antibodies identified in solid-phase antibody detection assays. While the implementation of cPRA and vXM is undoubtedly a major step forward in organ allocation algorithms, it is only the beginning of a long journey. Other compelling issues must still be considered and addressed, such as establishing appropriate threshold (cutoff) values for antibody assignment and recognizing the relevance of antibodies to histocompatiblity antigens historically ignored by the transplant community (i.e., HLA-Cw*, HLA-DQ* and HLA-DP* antigens). While new technologies have impacted allocation and outcome of transplanted kidneys, it is important to understand that these methodologies are not flawless.